This application is for a research scientist award that will continue to maximize efforts that can be expended in studies of the biological basis of drug abuse. Addictive disorders appear to result from the excessive use of reinforcers. Identification and characterization of the neurobiological substrates of reinforcement is necessary for understanding the biological basis of these disorders. Three research projects are in progress that directly address investigations of the mechanisms of cocaine and opiate reinforcement. It is generally accepted that DA is the mediator of the reinforcing effects of environmental events (including drug and non-drug reinforcers). This is a relatively limited hypothesis for the complex brain processes shown to be involved in reinforcement mechanisms. It is likely that a number of neuronal systems and brain loci are important to the processes underlying the compulsive use of:cocaine and heroin. The goal of this research proposal is the continued investigation of several neuronal systems involved in the self-administration of cocaine and heroin using neurotransmitter turnover rates, local cerebral glucose utilization, receptor binding, intracranial agonist and antagonist administration, neurotoxin lesions, antisense oligonucleotides and microdialysis. This broad based research approach will hopefully result in a greater understanding of the neurobiology of cocaine and heroin abuse and help in the identification of novel treatment approaches. The past funding of this application has permitted the candidate to spend significant effort on drug abuse research and research development. This award has assisted in the candidates ability to obtain salary support for hiring junior faculty that assumed major percentages of the teaching, administrative and service responsibilities that the applicant encountered. In addition, the released funds helped support an administrative secretary and administrative manager that assumed some of the time intensive day to day duties in the department to permit the applicant to concentrate more effectively on research efforts. In summary, this award has made and will hopefully, continue to make it possible for the applicant to devote significant time to research and research administration in the area of neurobiological mechanisms of the behavioral actions of abused drugs.